Secondary peripheral T-cell lymphoma in a patient with DLBCL harboring BLM mutation following CD19/CD22 bispecific CAR-T cell therapy

We describe a case of secondary peripheral T-cell lymphoma (PTCL) arising from infused CD19/CD22-4-1BB-CD3ζ-lenti bispecific chimeric antigen receptor (CAR)-T cells in a patient with relapsed or refractory B-cell lymphoma who carried a pathogenic germline BLM p.L107Ffs*36 variant. Integrated genomic and molecular analyses confirmed that the PTCL was clonally derived from the infused CAR-T product and revealed a multistep oncogenic process involving pre-existing driver mutations (BLM), somatic TET2 mutations (p.R1261H and p.E1755*), and genomic instability. Clonal CAR vector integration events in cancer-associated genes (NF1, CBX5, RNF213, etc) were identified as markers of clonal expansion, although no functional evidence supports a direct oncogenic role. We acknowledge that this case lies on a spectrum between clonal lymphoproliferative disorder and overt PTCL, and terminology continues to evolve. This case suggests a need for re-biopsy of suspected relapses after CAR-T therapy and highlights the limitations of conventional product assessment in detecting premalignant clones.